Parental confounders play significant role

Action Points

Note that this observational study using Swedish administrative data suggested an association between maternal antidepressant use and intellectual disability in children, but the relationship did not hold up to multivariable adjustment.

There may be genetic links between maternal depression and child intellectual disability that are yet unaccounted for.

Swedish researchers analyzing a large national registry could not identify a significant association between maternal use of antidepressants and neurodevelopmental abnormalities in their children.

After the researchers adjusted for potential parental confounders, use of antidepressants during pregnancy was found as only a non-significant trend toward increased risk of intellectual disability in the offspring (adjusted RR 1.33, 95% CI 0.90-1.98), reported Alexander Viktorin, PhD, of Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

The analysis included nearly 4,000 children of women using antidepressants during pregnancy, along with about 174,000 unexposed controls.

While a greater overall percentage of offspring exposed to antidepressants in utero had intellectual disabilities (0.9% of children) compared with unexposed offspring (0.5% of children), the association was likely attributed to other parental confounders, the authors wrote online in JAMA Psychiatry.

They described their findings as "the first to directly assess the [relative risk] of diagnosed [intellectual disability] in children born to mothers treated with antidepressants during pregnancy." The team said that intellectual disability (which the authors defined as "an IQ below 70, along with adaptive deficits that impair everyday functioning") not only has "immense social effects," but is also a common cause of healthcare-related societal costs.

For the study, Viktorin et al examined a birth cohort of Swedish children from the Swedish Medical Birth Register, and medication use was identified through the Swedish Prescribed Drug Register. Children were considered exposed if the mother had at least two dispensations of antidepressants with "medication periods that overlapped the pregnancy." Offspring with only one medication exposure were not considered exposed or unexposed and were analyzed separately.

Children were considered to have an intellectual disability if they had a "clinically ascertained diagnosis" in the Swedish National Patient Register (at least one inpatient or outpatient specialist care admission).

Overall, 179,007 children were included in the study, and 52% were boys (mean age of almost 8). Intellectual disability was diagnosed in 819 unexposed children and 37 exposed children. There were 3,982 children (2.2%) born to mothers with at least two dispensations for antidepressant medication. Of these women, nearly 80% were treated with selective serotonin reuptake inhibitors (SSRIs).

Unadjusted models found an overall increased likelihood of intellectual disability for exposed children of 97% (RR 1.97, 95% CI 1.42-2.74).

However, this association was attenuated when the authors adjusted for a variety of parental confounders, including:

However, when the researchers adjusted for age, father's use of medication, and education levels alone, the increased likelihood of intellectual disability was reduced from 97% to 66% (adjusted RR 1.66, 95% CI 1.17-2.34), leading the authors to speculate that "parental age and mother's psychiatric disorder" may play a larger role than antidepressant use alone.

When the authors examined relative risk among various types of antidepressants, there was a strong trend toward increased likelihood of intellectual disability among children whose mothers used SSRIs (adjusted RR 1.48, 95% CI 0.98-2.23) and a weaker trend among children whose mothers used non-antidepressant psychotropic medications (adjusted RR 1.31, 95% CI 0.75-2.27).

There was no clear relationship to disability among children with mothers who used non-SSRI antidepressants (adjusted RR 0.81, 95% CI 0.33-2.00).

The authors noted that because these analyses were comparable to analyses of children exposed to any antidepressant during pregnancy, this "further suggests that the underlying condition precipitating the medication is important" for the link between maternal antidepressant exposure in utero and intellectual disability in offspring.

Limitations to the study noted by the researchers included the fact that the Swedish Prescribed Drug Register collects only information about prescriptions but not about adherence to the drugs. In addition, the Swedish National Patient Register does not provide information from primary care, so patients diagnosed by primary care physicians may have gone undetected.

This study was sponsored by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health, the Beatrice and Samuel A. Seaver Foundation, and the Canadian and Swedish governments.

Viktorin reported having no conflicts of interest. Other co-authors disclosed support from Vencerx Therapeutics, Genentech, Ovid Therapeutics, Supernus Pharmaceuticals, and Shire Pharmaceuticals.

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